Cisplatin (CDDP) is a platinum complex having a wide anticancer spectrum and potent anti-tumor activity, and has contributed to the improvement of treatment results of various cancers as a key medicament in combination of multiple drugs for the treatment of solid cancers. However, cisplatin shows serious side effects such as serious nephrotoxic, nausea and vomiting, and further the existence of cancers being resistant against cisplatin becomes clinical problems for the treatment of cancers. Under these circumstances, it has been reported that a number of platinum complexes having 1,2-diaminocyclohexane (DACH) and 1,2-diaminocycloheptane as ligands do not show cross-resistance to cisplatin-resistant L1210 murine leukemia cells, and maintain their anti-tumor activity (cf. Jpn. J. Cancer Chemother., 10, pp 2442-2451 (1983)). However, in the research thereafter, there are cases wherein certain cisplatin resistant cancer cells shows sensitivity to platinum complexes having DACH ligand, but other cisplatin-resistant cancer cells show cross-resistance to the said platinum complexes having DACH ligand, or cases wherein certain cisplatin resistant cancer cells show sensitivity to certain platinum complexes but show cross-resistance to other platinum complexes (cf. Ann. Oncol., 2, 535-540 (1991); Cancer Research, 52, 5674-5680 (1992); ibid., 53, 4913-4919 (1993), etc.). The reasons therefor have been studied, and speculated to be due to the properties of each cell or the resistance mechanism thereof, but they have not been clarified yet.
The mechanism of having resistance of cancer cells to platinum complexes such as cisplatin may be, for example, decrease in the uptake of platinum into cells, increase in glutathione and metallothionein level as intracellular detoxication, increase of DNA repair ability, increase of permissibility to DNA injury, etc. (cf., Biochem. Pharmacol., 30, 2721-2723 (1981); Br. J. Cancer, 54, 239-243 (1986); Cancer Lett., 31, 163-169 (1986); Biochem. Pharmacol., 52, 1855-1865 (1996)).
It has been reported that a liposome preparation containing cis-bis(neodecanoato)-(1R,2R)-1,2-diamino-cyclohexane platinum (II) are more effective to cisplatin-resistant cancers (cf., Cancer Research, 48, 4509-4512 (1988); ibid., 53, 4913-4919 (1993)).
It has been reported that a preparation (SM-11355/LPD), which is prepared by suspending the following cis[((1R,2R)-1,2-cyclohexanediamine-N,N′)bis(myristato)]platinum (II) (abbreviated as SM-11355) in an iodized poppyseed oil fatty acid ethyl ester (Lipiodol™: abbreviated as LPD), showed potent anti-tumor effects in a rat hepatic cancer model and rabbit VX-2 transplantable hepatic cancer model by administering to the hepatic artery, where the platinum complex is retained in the hepatic cancer tissues for a prolonged period and thereby is gradually released (cf., Ono et al., J. Jpn. Soc. Cancer Ther., 27, 49-58 (1992); Kishimoto et al., Drug Delivery Systems, 5, 243-247 (1990); Kishimoto et al,. Reg. Cancer Treat., 1-2, 25-29 (1992)); Kishimoto et al., Biol. Pharm. Bull., 23, 344-348 (2000)).
